EXCHANGE 


*pn> 


The  Preparation  and  Properties  of  Sevei 
Phenyl  Alkyl  Succinic  Acids 


THEOS  JEFFERSON  THOMPSON 


A  THESIS 


PRESENTED  TO  THE  FACULTY  OF 

THE  GRADUATE  COLLEGE  IN  THE  UNIVERSITY  OF  NEBRASKA 

IN  PARTIAL  FULFILLMENT  OF  THE  REQUIREMENTS 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY 


DEPARTMENT  OF  CHEMISTRY 


Lincoln,  Nebraska, 
1921 


The  Preparation  and  Properties  of  Several 
Phenyl  Alkyi  Succinic  Acids 


THEOS  JEFFERSON  THOMPSON 


A  THESIS 


PRESENTED  TO  THE  FACULTY  OF 

THE  GRADUATE  COLLEGE  IN  THE  UNIVERSITY  OF  NEBRASKA 

IX  PARTIAL  FULFILLMENT  OF  THE  REQUIREMENTS 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY 


DEPARTMENT  OF  CHEMISTRY 


Lincoln,  Nebraska, 
1921 


ACKNOWLEDGMENT 

The  author  desires  to  express  his  sincere  gratitude  to  Doctor  Fred.  W . 
Upson,  under  whom  this  investigation  was  carried  on,  for  his  unfailing 
interest  and  valuable  assistance. 


THE  PREPARATION  AND  PROPERTIES  OF  SEVERAL  PHENYL 
ALKYL   SUCCINIC  ACIDS. 

The  original  purpose  of  this  investigation  was  the  separation  of  the  optical 
isomers  of  ^'sopropyl-phenyl-succinic  acid  prepared  by  A  very  and  Upson.1 
To  the  present  time  this  has  not  been  accomplished  although  resolution 
was  attempted  with  brucine,  quinine,  strychnine  and  cinchonine.  During 
the  course  of  the  attempted  resolutions,  however,  a  number  of  incidental 
questions  arose.  Among  these  were  the  preparation  of  other  substituted 
succinic  acids,  the  difficulty  of  saponification  of  the  nitrils  of  certain  sub- 
stituted succinic  acids  already  referred  to  by  Avery  and  Upson,  and  the 
structure  of  the  sodium  benzyl  compound  which  results  from  the  interac- 
tion of  sodium  amide  and  benzyl  cyanide. 

I.  Preparation  of  Nitrils. 

Preparation  of  alkyl  phenyl-succino-nitril  and  of  alkyl  phenyl-succino- 
half-nitril  half-ester  was  carried  out  by  condensing  alkyl  cyanohydrines 
with  benzyl  cyanide  by  means  of  (1)  sodium  ethoxide,  or  methoxide  and 
(2)  esters  of  a-bromo  fatty  acids  with  benzyl  cyanide  by  means  of  sodamide, 
respectively. 

1.  Alkyl  Aldehyde  Cyanohydrines  with  Benzyl  Cyanide.  Discussion. 
— When  it  was  determined  that  zsopropyl-phenyl-succinic  acid  could  not 
be  resolved,  an  attempt  was  made  to  prepare  other  substituted  succinic 
acids,  in  the  belief  that  optically  active  compounds  might  be  resolved  from 
them.  The  method  of  condensation  employed  was  a  modification  of  the 
one  used  by  Avery  and  Upson1  in  the  preparation  of  f'sepropyl-phenyl- 
succino-nitril.  The  condensations  of  the  cyanohydrines  of  acetic  aldehyde, 
n-propionic  aldehyde,  acetone,  methylethyl-ketone  and  wovaleric  alde- 
hyde with  benzyl  cyanide  were  attempted  in  the  order  mentioned;  but 
i50valeric-cyanohydrine  was  the  only  one  that  gave  a  condensation  com- 
pound. The  yield  was  very  good  in  the  case  of  the  ^sovaleric  -phenyl-suc- 
cino-nitril; also  hi  the  case  of  wopropyl-phenyl-succino-nitril.  As  yet  we 
1  Avery  and  Upson,  J.  Am.  Chem.  Soc.,  30,  600  (1908). 


have  been  unable  to  determine  why  we  could  not  secure  favorable  results 
from  the  other  cyanohydrines.  It  was  first  thought,  as  suggested  by 
Higson  and  Thorpe,2  that  the  proportional  amount  of  sodium  used  was  too 
large,  but  this  was  reduced  far  below  the  equimolecular  proportion  with 
the  same  results. 

Experimental.  —  Since  the  operations  in  each  case  were  in  the  main  the  same, 
only  the  condensation  of  isovaleric-cyanohydrine  with  benzyl  cyanide  will  be  described. 

Eight  g.  of  benzyl  cyanide  was  added  to  1.5  g.  of  sodium,  which  had  been  dissolved 
in  an  excess  of  methyl  alcohol.  To  the  sodium  methoxide-benzyl  cyanide  solution, 
8  g.  of  isovaleric-aldehyde-cyanohydrine  was  added.  The  mixture  wa  shaken  several 
times  and  allowed  to  stand  for  several  hours,  whereupon  large  cyrstals  of  the  wovaleric 
phenyl-succino-nitril  separated. 

H  Na  H 


+  NaOH 

OH  H  R—  C—  C  =  N 

I 
H 

When  it  was  believed  that  crystallization  was  complete,  the  crystals  were  collected,  and 
dissolved  hi  hot  methyl  alcohol.  After  this  solution  cooled,  water  was  added  until 
crystallization  of  the  nitril  occurred.  The  crystals  were  dried  and  weighed.  Yield, 
84%,  much  better  than  the  yield  obtained  by  A  very  and  Upson.  Ethyl  alcohol  may 
be  used  in  place  of  methanol,  but  is  slower  in  reaction  and  the  yield  is  slightly  less. 

2.  Ethyl  Esters  of  Alpha-bromo  Fatty  Acids  with  Benzyl  Cyanide. 
Discussion.  —  In  1910  Bodroux  and  Taboury3  allowed  sodamide  to  react 
with  benzyl  cyanide  suspended  in  ether.  By  means  of  the  reaction  of 
alkyl  halides  on  this  sodium  benzyl  cyanide,  they  were  able  to  prepare  a 
number  of  derivatives.  This  method  was  adapted  to  the  preparation  of 
the  substituted  succinic  acids,  if  a-bromo  fatty  acid  esters  were  used  in 
place  of  alkyl  halides.  In  each  reaction  attempted,  more  or  less  satis- 
factory results  were  obtained.  The  yield  was  generally  quite  low. 

Experimental.  —  Four  g.  of  finely  powdered  sodamide  was  suspended  in  40  cc.  of 
absolute  ether  and  to  this  12  g.  of  benzyl  cyanide  was  added  in  small  amounts  while 
the  reaction  mixture  was  cooled  by  running  water.  A  moderate  reaction  occurred. 
Ammonia  was  evolved  and  the  solution  assumed  a  color  varying  from  amber  to  red. 
After  the  reaction  had  subsided,  the  mixture  was  refluxed  for  12  hours.  To  the  sodium 
benzyl  cyanide  compound  21  g.  of  ethyl  a-bromo-wovalerate  was  added  in  small  amounts 
while  the  reaction  flask  was  cooled  in  running  water.  After  a  vigorous  reaction,  the 
mixture  set  to  a  jelly-like  mass.  A  large  excess  of  absolute  ether  was  added  and  the 
mixture  was  refluxed  for  24  hours. 

Na  H 

=  N  —  >  <(        )>  _c_C  =  N      +  NaBr 

R—  C—  C—  OR 

I      II 
H     O 


/ \ 

R— C— C— OR  +    <^ ^> 


2  Higson  and  Thorpe,  J.  Chem,  Soc.,  89,  1455  (1906). 

3  Bodroux  and  Taboury,  Compt.  rend.,  150,  531-3  (1910). 


When  the  reaction  was  complete,  the  ether  solution  was  acidified  with  dil.  hydrochloric 
acid.  At  this  point,  when  an  excess  of  sodamide  was  added,  crystals  of  the  half  acid 
or  dibasic  acid  separated.  Whether  they  were  the  half-acid,  or  the  dibasic  acid, 
depended  upon  the  character  of  the  substituted  groups.  This  will  be  discussed  later. 
Usually  an  excess  of  sodamide  was  avoided  and  the  acid  solution  was  extracted  several 
times  with  ether.  Evaporation  of  the  ether  under  diminished  pressure  on  the  boiling 
water-bath  left  an  oily  viscous  residue  in  the  flask.  When  cone,  hydrochloric  acid  was 
added  and  the  condensation  product  was  refluxed  for  8  hours,  most  of  the  oily  residue 
disappeared ;  and,  as  the  product  cooled,  small  crystals  separated.  Since  these  crystals 
were  insoluble  in  benzol,  it  was  possible  to  extract  the  non-hydrolyzed  residue,  to  evapo- 
rate the  benzol  under  diminished  pressure,  and  to  continue  the  hydrolysis  as  before. 
Then  the  crystals  were  filtered  from  the  diluted  hydrochloric  acid  solution,  dried,  and 
dissolved  in  hot  alcohol.  The  alcohol  solut  on  was  cooled  and  water  added,  whereupon 
crystals  separated;  m.  p.  (uncorr.)  172°.  Titration  of  0.0910  g.  required  38.3  cc.  of 
0.01  N  sodium  hydroxide  solution;  the  calculated  amount  for  one  hydrogen  is  41.7  cc. 

The  crystals  gave  a  positive  test  for  nitrogen.  The  titration  indicated  that  the 
compound  had  been  hydrolyzed  only  partially.  Since  irregularity  in  saponification 
had  already  been  observed,2  the  half -acid  was  placed  in  a  bomb  tube  with  cone,  hydro- 
chloric acid  and  heated  at  135°  for  24  hours.  The  crystalline  substance  obtained  was 
washed  into  a  beaker,  and  diluted  with  water  to  dissolve  ammonium  chloride.  The 
crystals  were  then  collected  and  dissolved  in  the  smallest  amount  of  hot  alcohol.  The 
addition  of  a  large  amount  of  cold  water  caused  a  copious  crop  of  crystals  to  separate 
which  melted  sharply  at  178°.  Titration  of  0.0722  g.  required  59.0  cc.  of  0.01  N  sodium 
hydroxide  solution;  the  calculated  for  two  replaceable  hydrogens  is  61.2  cc.  The  yield 
was  poor.  A  qualitative  test  for  nitrogen  was  negative. 

A  mixed-melting-point  determination  was  made  with  the  acids  obtained  from  ethyl 
a-bromo-i5ovalerate  and  tsobutyl-aldehyde-cyanohydrine  condensation  compounds 
with  benzyl  cyanide.  This  mixture  melted  sharply  at  178°,  and  therefore  the  com- 
pounds resulting  from  the  two  methods  of  preparation  are  identical. 

When  the  hydrolysis  was  not  attempted  by  means  of  refluxing  but  the  oily  residue 
was  placed  immediately  in  the  bomb  tubes,  the  crystals  were  found  to  be  enveloped  in 
an  oily  viscous  mass  which  could  be  removed  by  shaking  them  with  benzene. 

This  same  method  has  been  applied  in  the  preparation  of  the  following 
new  substituted  succinic  acids,  in  addition  to  the  one  already  discussed: 
(1)  w-propyl-phenyl -succinic  acid,  prepared  from  ethyl  a-bromo-w-valerate 
and  benzyl  cyanide;  (2)  ethyl-phenyl-succinic  acid,  prepared  from  ethyl 
a-bromo-n-butyrate  and  benzyl  cyanide;  (3)  methyl-phenyl-succinic  acid, 
prepared  from  ethyl  a-bromo-propionate  and  benzyl  cyanide. 

II.  Saponification. 

Discussion. — It  had  been  observed  by  Avery  and  Upson  that  the 
saponification  of  ^opropyl-phenyl-succino-nitril  was  difficult.  A  similar 
difficulty  of  saponification  of  diphenyl-succino-nitril  has  been  noted  by 
a  number  of  investigators.4  So  far  as  we  have  been  able  to  determine,. 
4  Reimer,  (Ber.,  14,  1802  (1881))  in  speaking  of  saponifying  dicyano-dibenzyl  says: 
"Upon  heating  with  alcoholic  potassium  hydroxide  the  substance  yielded  besides  a 

resinous  product  only  a  very  slight  amount  of  acid A  more  sucessful 

saponification  was  accomplished  by  heating  with  concentrated  hydrochloric  acid  at  200°." 
Chalonay  and  Knoevenagel  (Ber.,  25,  289  (1892))  say:    "By  heating  the  substance 


diphenyl-succino-nitril  has  never  been  hydrolyzed  satisfactorily  except 
under  pressure  at  high  temperatures.  We  believe  this  fact  indicates  a 
steric  hindrance  effect.  This  deduction  is  further  borne  out  by  the  present 
investigation,  because  it  has  been  impossible  to  saponify  iso-propy\- 
phenyl-succino-nitril  and  wobutyl-phenyl-succino-nitril  further  than  the 
half-acid  by  the  usual  methods;  while  n-propyl-,  ethyl-  and  methyl-phenyl- 
succino-nitril  are  saponified  with  increasing  ease  by  the  usual  methods. 
It  should  be  noted  that  when  the  half-nitril  half-ester  of  isobutyl  or  iso- 
propyl-phenyl-succinic  acid  was  saponified,  the  nitril  group  remained 
intact,  and  from  the  method  of  condensation,  this  nitril  group  must  be  ad- 
jacent to  the  phenyl  group.  The  preparation  of  a  compound  with  an 
ester  group  adjacent  to  the  phenyl  was  attempted  by  condensing  ethyl 
ester  of  phenyl-bromo-acetic  acid  with  aliphatic  nitrils,  but,  as  yet,  positive 
results  have  not  been  obtained.  It  was  hoped  that  this  compound  could 
be  prepared  so  that  we  might  determine,  in  a  measure  at  least,  whether 
the  difficulty  of  saponificatkm  is  entirely  one  of  steric  hindrance,  or  both 
steric  hindrance  and  resistivity  of  the  nitril  group  to  saponification.  In 
this  connection  Wren  and  Still5  say:  "The  saponification  of  alpha  (racemic) 
ethyl  diphenyl-succinate  with  aqueous  alcoholic  potassium  hydroxide 

proceeds  normally "     This  would  indicate  that  the  character  of  the 

nitril  group  as  compared  with  the  ester  group  entered  into  the  question 
of  saponification.  Sulo  Kilpi6  after  studying  the  rate  of  hydrolysis  of 
aceto-,  propiono-,  n-butyro-  and  n-valero-nitrils  with  hydrochloric  acid 
and  alcohol  and  aqueous  alkali  states;  "The  velocity  of  hydrolysis  increases 
in  the  same  direction  as  does  the  negative  character  of  the  carbon  atom  of 
the  carbonyl  group  determined  according  to  the  system  of  Michael." 
Although  an  accurate  determination  of  the  velocity  of  hydrolysis  was  not 
made,  it  has  been  definitely  shown  that  the  speed  and  ultimate  complete 
saponification  depends  upon  the  character  of  the  alkyl  groups  introduced. 
Whether  the  results  are  best  explained  by  Michael's  system,  or  on  the 
basis  of  a  steric  hindrance  effect,  we  cannot  say  at  the  present  time. 
Either  theory  seems  to  offer  a  satisfactory  explanation  of  the  observed 
facts. 

Experimental. 

Hydrolysis  of  Iso-propyl-phenyl-succino-nitril  by  the  Usual  Methods. 

(1)  Five  g.  of  wopropyl-phenyl-succino-nitril  was  refluxed  with  a  30%  solution 
of  sodium  hydroxide  for  8  hours.     At  this  time,  a  portion  of  the  solution  was  with- 

(diphenyl-succinonitril)  with  concentrated  hydrochloric  acid  at  150—160°  diphenyl- 
succinic  acid  melting  at  229-230°  was  obtained." 

Wren  and  Still  (J.  Chpm.  Soc.,  107,  445  (1915))  report:  "It  was  further  found 
that  the  hydrolysis  of  diphenyl-succinonitril  at  200°  by  means  of  aqueous  hydrochloric 
acid  leads  to  the  formation  of  meso-diphenyl-succinic  acid  " 

5  Ref.  5,  p.  444. 

'Kilpi,  Z.  physik.  Chem.,  86,  641-81  (1914). 


drawn  and  acidified  with  hydrochloric  acid,  whereupon  crystals  separated.  The  crystals 
were  dissolved  in  alcohol  and  when  titrated  indicated  only  a  trace  of  acid.  The  refluxing 
was  continued  for  10  hours,  when  0.0526  g.  required  1.9  cc.  of  0.1  N  sodium  hydroxide 
for  neutralization;  calc.  for  half-acid,  2.4  cc.  The  mixture  was  refluxed  again  for  8 
hours,  and  upon  titration  indicated  the  presence  of  the  half-acid.  Further  refluxing 
failed  to  hydrolyze  the  second  nitril  group. 

(2)  Five  g.  of  the  nitril  was  placed  in  a  flask  and  100  cc.  of  95%  alcohol  added. 
Fifteen  g.  of  solid  sodium  hydroxide  was  added  to  the  alcohol  solution  and  the  whole 
refluxed  for  12  hours.     The  alcohol  was  removed  by  vacuum  distillation  and  the  residue 
acidified  with  hydrochloric  acid  just  dilute  enough  to  dissolve  the  ammonium  chloride. 
As  in  the  first  case,  when  the  solution  was  acidified,  a  crystalline  substance  separated 
which,   when  titrated,  showed  the  presence  of  one  replaceable  hydrogen.     Further 
treatment  with  alcoholic  sodium  hydroxide  gave  the  same  result. 

(3)  Five  g.  of  the  nitril  was  dissolved  in  25  cc.  of  methyl  alcohol   and    an    equal 
amount  of  water,  to  which  was  added  5  g.  of  sodium  hydroxide.     After  this  solution 
had  been  refluxed  for  8  hours,  0.1143  g.  required  3.2  cc.  of  0.1  N  sodium  hydroxide 
solution  for  neutralization;  calc.  for  one  acid  group,  5.13  cc.     The  refluxing  was  con- 
tinued for  30  hours  longer,  but  hydrolysis  could  not  be  carried  beyond  the  half-acid 
stage. 

(4)  Five  g.  of  the  acid  was  placed  in  a  flask  with    100  cc.   of  cone,  hydrochloric 
acid  and  the  whole  refluxed  for  2  hours,  when  the  water  and  acid  were  evaporated  under 
diminished  pressure.     The  residue  was  treated  again  with  100  cc.  of  cone,  hydrochloric 
acid  and  refluxed  for  8  hours.     The  crystals  which  separated  from  the  cold  dil.  hydro- 
chloric acid  solution  proved  to  be  the  half-acid. 

Hydrolysis  in  every  case  was  best  brought  about  by  the  use  of  cone,  hydrochloric 
acid.  It  was  possible  to  hydrolyze  completely  the  half-ester  half-nitril  of  n-propyl- 
phenyl-,  ethyl-phenyl-  and  methyl-phenyl-succinic  acid  in  16,  10  and  4  hours,  respec- 
tively. The  half-ester  half-nitril  of  tsopropyl-phenyl-succinic  acid  was  hydrolyzed  in 
much  the  same  manner  as  the  nitril  and  to  the  same  degree.  However,  the  ester  group 
appeared  to  be  more  easily  hydrolyzed  than  the  corresponding  nitril  group. 

III.  Analysis  and  Properties  of  the  Acids. 

The  acids  are  soluble  in  alcohol  and  ether  and  insoluble  in  cold  water, 
benzol,  petroleum  ether,  and  chloroform.  Their  solubility  in  alcohol  is  a 
function  of  the  number  and  relative  positions  of  the  carbons  of  the  sub- 
stituted alkyl  groups.  Methyl-phenyl-succinic  acid  is  readily  soluble  in 

TABLE  I 
ANALYSES,  MELTING  POINTS  AND  SOLUBILITIES  OF  THE  Acros7 

Solubility    in 
100  g.  water 

at  25° 
Acid  Hydrogen  Carbon          M.  p.  X  10* 

Calc.     Found       Calc.       Found 
%  %  %  %  °C.  G. 

«50Butyl-phenyl-succinic  acid 7.02  7.11  67.02  66.84  183.4  13.3 

t50Propyl-phenyl-succinic  acid 6.77  7.05  66.1  66.16  178  20.6 

n-Propyl-phenyl-succinic  acid 6.77  6.87  66.1  66.00  213                     2.11 

Ethyl-phenyl-succinic  acid 6  . 30  6.51  64 . 86  64 . 53  196  10 . 5 

Methyl-phenyl-succinic  acid 5.73  5.89  63.41  63.71  182  41.1 

7  Analyses  by  F.  L.  Herman  and  L.  Porter. 


8 

cold  methyl  or  ethyl  alcohol  and  cannot  be  precipitated  from  alcohol  solu- 
tions by  the  addition  of  cold  water  as  can  the  other  acids  of  the  series. 
It  can  be  purified  only  by  recrystallization  from  hot  water.  Microscopic 
examination  of  the  crystals  of  the  acids  shows  that  each  one  possesses  a 
characteristic  crystalline  form.  The  crystals  of  ^sopropyl-phenyl-succinic 
acid  are  especially  beautiful. 

Four  determinations  of  the  molecular  weight  of  ^opropyl-phenyl- 
succinic  acid  were  made  by  the  boiling-point  method.  The  molecular 
weight  determined  from  an  average  of  the  four  is  241  ;  that  calculated,  236. 

Structure  of  Sodium  Benzyl-Cyanide  Compound. 

During  the  course  of  this  investigation,  a  deposit  of  the  sodium  com- 
pound, formed  by  sodamide  with  benzyl  cyanide  in  ether  solution,  was 
accidentally  allowed  to  stand  on  a  filter  paper.  When  the  ether  evaporated 
auto-oxidation  took  place  accompanied  by  considerable  heat  evolution. 
The  heat  of  the  reaction  was  sufiicient  to  decompose  the  filter  paper  com- 
pletely wherever  the  residue  came  in  contact  with  it.  It  is  thought  the 
decomposition  of  a  slight  excess  of  sodamide  liberated  sufficient  heat  to 
start  an  auto-oxidation.  Since  such  auto-oxidation  reactions  are  in  general 
characteristic  of  unsaturated  compounds,  we  believe  that  the  results  ob- 
served indicate  a  state  of  unsaturation.  The  residue  left  after  the  reaction 
was  complete  was  yellow  in  color  with  a  cork-like  texture. 

A  portion  of  the  product  was  shaken  with  water  in  which  it  dissolved 
to  give  a  clear  solution.  A  small  amount  of  the  water  solution  gave  a 
very  positive  reaction  for  sodium  cyanide.  Since  the  water  solution  showed 
no  trace  of  immiscible  liquids,  such  as  benzyl  cyanide,  benzyl  alcohol,  or 
benzaldehyde.  it  was  concluded  that  the  remainder  of  the  sodium  benzyl- 
cyanide  compound  either  must  have  volatilized  during  the  auto-oxidation, 
or  must  be  present  in  the  residue  in  a  soluble  form.  A  small  quantity  of 
the  cork-like  residue  was  placed  in  a  distilling  flask  and  heated  on  an  oil- 
bath.  The  temperature  was  raised  gradually  until  as  it  approached  125° 
small  crystals  began  to  collect  on  the  neck  of  the  flask.  The  heating  was 
continued  until  the  temperature  reached  180°.  The  crystals  were  re- 
crystallized  from  hot  water  and  proved  to  be  benzoic  acid.  In  view  of 
these  facts  we  suggest  Formula  I  for  the  sodium  benzyl  cyanide  compound, 
H  Na 

1  y      ' 

-C  =  C  =  N—  Na        / 


(I).  (II). 

and  we  believe  the  results  observed  can  be  explained  better  by  this  formula 
than  by  Formula  II  at  present  current  in  the  literature. 

In  conclusion  the  facts  seem  to  indicate  that  a  state  of  unsaturation 


exists  in  the  compound,  and  since  the  presence  of  sodium  cyanide  and 
benzoic  acid  has  been  shown,  this  unsaturation  must  exist  between  the 
carbon  atoms. 

The  results  and  vigorousness  of  the  reaction  are  probably  best  explained 
by  (1)  assuming  that  the  unsaturation  promotes  the  absorption  of  oxygen 
and  the  cleavage  of  the  compound  into  benzaldehyde  and  sodium  iso- 
cyanide,  which  always  exist  in  equilibrium  with  sodium  cyanide,  cleavage 
at  the  ethenoid  linkage  being  a  common  reaction  especially  in  the  presence 
of  alkalies  ;  (2)  the  fact  that  benzaldehyde  hi  the  presence  of  air,  it  is  known, 
readily  absorbs  oxygen  forming  benzoyl  hydrogen  peroxide  ;  and  (3)  the 
belief  that  the  peroxide  thus  formed,  being  a  very  active  oxidizing  agent, 
interacts  with  benzaldehyde  forming  benzoic  acid,  thus  accounting  for  the 
vigorousness  of  the  reaction. 

A  simple  explanation  of  the  condensation  reaction  on  the  basis  of  the 
iso  structure  of  the  sodium  benzyl  cyanide  compound  is  suggested  by 
Nef's8  ideas  of  the  aceto-acetic  ester  and  aldol  condensations. 

The  condensation  reactions  are  therefore  outlined  thus,  using  the  sug- 
gested formula. 

1.  The  bromo  ester  dissociates  hydrogen  bromide. 

Br    o  **    O 

I       •  >*     I 

R—  C—  C—  OR  5=t  R—  C  -  C—  OR  +  HBr. 

2.  Hydrogen  bromide  reacts  on  the  sodium  benzyl-cyanide  giving  a  ketene-imide 
structure. 

H  H 


=C=N—  |Na|  +  HlBrl  —  C  =  C=N—  H  -f  NaBr 

~    — 


3.  The  ketene-imide  adds  to  the  alkylidene  derivative  of  the  ester  at  the  same  time 
undergoing  rearrangement  as  follows. 

—  *-  -<  --  1 
R-C  —  > 

^   +  H-N=C=C- 
=  C-OR   \  _ 

R—  C—  H 

I 
O  =  C—  OR. 

The  work  on  the  structure  and  properties  of  other  metallic  derivatives 
of  benzyl  cyanide  is  being  continued. 

Summary. 

1.  The  following  new  substituted  succinic  acids  were  prepared:     (1) 
methyl-phenyl-succinic  acid,  (2)  ethyl-phenyl-succinic  acid,  (3)  w-propyl- 
phenyl-succinic  acid,  (4)  fsobutyl-phenyl-succinic  acid. 
5Ref.  Ann.,  298,  218  (1897). 


10 

2.  The  preparation  of  the  acid  was  brought  about  by  two  operations  : 
(1)  the  condensation  of  molecules  of  proper  constitution  in  the  molecular 
proportions  to  synthesize  the  desired  nitril  or  ester;  (2)  the  hydrolysis 
of  the  nitril  or  ester. 

3.  Two  methods  were  used  to  bring  about  the  condensation:    (1)  al- 
dehydes of  the  fatty  acid  series  were  converted  to  the  cyanohydrines  and 
condensed  with  benzyl  cyanide  by  means  of  sodium  ethoxide  or  sodium 
methoxide;  (2)  esters  of  a-bromo  fatty  acids  were  condensed  with  benzyl 
cyanide  by  means  of  sodamide. 

4.  The  complete  hydrolysis  of  the  nitrils  or  esters  of  wopropyl-  and*50- 
butyl-phenyl-succinic  acid  cannot  be  brought  about  by  the  usual  acid  or 
alkali  methods,  but  these  substances  must  be  heated  in  a  bomb  tube  at 
130-140  °  for  from  24  to  30  hours.    This  resistance  to  hydrolysis  is  probably 
due  to  a  steric  hindrance  effect,  to  an  electrochemical  effect  of  the  sub- 
stituted alkyl  group,  or  to  a  combination  of  the  two  effects 

5.  The  general  properties  of  each  acid  vary  according  to  its  constitution. 

6.  A  new  formula  is  suggested  for  the  compound  formed  when  sodamide 
reacts  with  benzyl  cyanide  in  ether  solution. 


p 


UNIVERSITY  OF  CALIFORNIA  LIBRARY 


